open access

Vol 85, No 6 (2017)
ORIGINAL PAPERS
Published online: 2017-12-14
Submitted: 2017-10-20
Accepted: 2017-11-26
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Histone deacetylases affect transcriptional regulation of CCL2 and CXCL8 expression by pulmonary fibroblasts in vitro

Paweł Golec, Paweł Leszek Bernatowicz, Grażyna Tokajuk, Mirosław Kozłowski, Krzysztof Kowal
DOI: 10.5603/ARM.2017.0053
·
Adv Respir Med 2017;85(6):307-312.

open access

Vol 85, No 6 (2017)
ORIGINAL PAPERS
Published online: 2017-12-14
Submitted: 2017-10-20
Accepted: 2017-11-26

Abstract

Introduction: Chemokines have been shown to play an important role in tissue remodeling and fibrosis in the respiratory system. In this study we wanted to evaluate the mechanisms, which regulate the expression of selected chemokines by pulmonary fibroblasts in vitro. Material and methods: Pulmonary fibroblasts were cultured with and without bacterial lipopolysaccharide (LPS) for 6 hours. In addition some of the cultures were pre-treated with histone deacetylase inhibitor Trichostatin A (TSA). Real-time PCR reaction was performed to estimate the expression of chemokines CCL2, CCL3 and CXCL8. Results: In unstimulated cultures detectable expression of CCL2 and CXCL8 was observed, while CCL3 expression could not be detected. After stimulation with LPS, TSA and both agents together CCL2 expression rose by 1.52, 1.62 and 1.8 times in comparison to control cultures respectively. CXCL8 mRNA expression levels after stimulation with LPS, TSA and LPSTSA increased by 1.53, 1.91 and 2.4 times accordingly. Conclusion: Epigenetic mechanisms related to histone acetylation affects transcriptional regulation of CCL2 and CXCL8 expression by pulmonary fibroblasts. Those mechanisms may play a role in tissue repair and pathologic remodeling.

Abstract

Introduction: Chemokines have been shown to play an important role in tissue remodeling and fibrosis in the respiratory system. In this study we wanted to evaluate the mechanisms, which regulate the expression of selected chemokines by pulmonary fibroblasts in vitro. Material and methods: Pulmonary fibroblasts were cultured with and without bacterial lipopolysaccharide (LPS) for 6 hours. In addition some of the cultures were pre-treated with histone deacetylase inhibitor Trichostatin A (TSA). Real-time PCR reaction was performed to estimate the expression of chemokines CCL2, CCL3 and CXCL8. Results: In unstimulated cultures detectable expression of CCL2 and CXCL8 was observed, while CCL3 expression could not be detected. After stimulation with LPS, TSA and both agents together CCL2 expression rose by 1.52, 1.62 and 1.8 times in comparison to control cultures respectively. CXCL8 mRNA expression levels after stimulation with LPS, TSA and LPSTSA increased by 1.53, 1.91 and 2.4 times accordingly. Conclusion: Epigenetic mechanisms related to histone acetylation affects transcriptional regulation of CCL2 and CXCL8 expression by pulmonary fibroblasts. Those mechanisms may play a role in tissue repair and pathologic remodeling.
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Keywords

CCL2, CXCL8, histone deacetylase inhibitors, fibroblasts, real-time polymerase chain reaction

About this article
Title

Histone deacetylases affect transcriptional regulation of CCL2 and CXCL8 expression by pulmonary fibroblasts in vitro

Journal

Advances in Respiratory Medicine

Issue

Vol 85, No 6 (2017)

Pages

307-312

Published online

2017-12-14

DOI

10.5603/ARM.2017.0053

Bibliographic record

Adv Respir Med 2017;85(6):307-312.

Keywords

CCL2
CXCL8
histone deacetylase inhibitors
fibroblasts
real-time polymerase chain reaction

Authors

Paweł Golec
Paweł Leszek Bernatowicz
Grażyna Tokajuk
Mirosław Kozłowski
Krzysztof Kowal

References (30)
  1. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007; 25(1): 9–18.
  2. Todd NW, Luzina IG, Atamas SP. Molecular and cellular mechanisms of pulmonary fibrosis. Fibrogenesis Tissue Repair. 2012; 5(1): 11.
  3. World Health Organization. Global Surveillance, Prevention and Control of Chronic Respiratory Diseases. A Comprehensive Approach. Geneva: World Health Organization. 2007.
  4. Speer C P, Speer CP, Thomas W, et al. Inflammation and bronchopulmonary dysplasia. Semin Neonatol. 2003; 8(1): 29–38.
  5. Fries KM, Blieden T, Looney RJ, et al. Evidence of fibroblast heterogeneity and the role of fibroblast subpopulations in fibrosis. Clin Immunol Immunopathol. 1994; 72(3): 283–292.
  6. Phipps RP, Borrello MA, Blieden TM. Fibroblast heterogeneity in the periodontium and other tissues. J Periodontal Res. 1997; 32(1 Pt 2): 159–165.
  7. Borsi L, Balza E, Allemanni G, et al. Differential expression of the fibronectin isoform containing the ED-B oncofetal domain in normal human fibroblast cell lines originating from different tissues. Exp Cell Res. 1992; 199(1): 98–105.
  8. Parsonage G, Falciani F, Burman A, et al. Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns. Thromb Haemost. 2003; 90(4): 688–697.
  9. Chang HY, Chi JT, Dudoit S, et al. Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci U S A. 2002; 99(20): 12877–12882.
  10. Schmidt M, Sun G, Stacey MA, et al. Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J Immunol. 2003; 171(1): 380–389.
  11. Prasad S, Hogaboam CM, Jarai G. Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair. Fibrogenesis Tissue Repair. 2014; 7: 7.
  12. Distler O, Pap T, Kowal-Bielecka O, et al. Overexpression of monocyte chemoattractant protein 1 in systemic sclerosis: role of platelet-derived growth factor and effects on monocyte chemotaxis and collagen synthesis. Arthritis Rheum. 2001; 44(11): 2665–2678.
  13. Kowal K, Bielecki M, Sacharzewska E, et al. Augmented in vitro expression of CCL2 by peripheral blood mononuclear cells is associated with the presence of interstitial lung disease in patients with systemic sclerosis. Reumatologia/Rheumatology. 2013; 3: 179–184.
  14. Kowal K, Moniuszko M, Dabrowska M, et al. Allergen challenge differentially affects the number of circulating monocyte subsets. Scand J Immunol. 2012; 75(5): 531–539.
  15. Richards TJ, Kaminski N, Baribaud F, et al. Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012; 185(1): 67–76.
  16. van Dijk EM, Menzen MH, Spanjer AIR, et al. Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2016; 310(11): L1166–L1176.
  17. Fernández-Bertolín L, Mullol J, Fuentes-Prado M, et al. Effect of lipopolysaccharide on glucocorticoid receptor function in control nasal mucosa fibroblasts and in fibroblasts from patients with chronic rhinosinusitis with nasal polyps and asthma. PLoS One. 2015; 10(5): e0125443.
  18. Fabisiak JP, Gao F, Thomson RG, et al. Mycoplasma fermentans and TNF-beta interact to amplify immune-modulating cytokines in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2006; 291(4): L781–L793.
  19. Szalai C, Kozma GT, Nagy A, et al. Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. J Allergy Clin Immunol. 2001; 108(3): 375–381.
  20. Tucci M, Barnes EV, Sobel ES, et al. Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis. Arthritis Rheum. 2004; 50(6): 1842–1849.
  21. Deng X, Zhou X, Deng Y, et al. Thrombin Induces CCL2 Expression in Human Lung Fibroblasts via p300 Mediated Histone Acetylation and NF-KappaB Activation. J Cell Biochem. 2017; 118(11): 4012–4019.
  22. Salim PH, Jobim M, Bredemeier M, et al. Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis. Cytokine. 2012; 60(2): 473–477.
  23. Deng X, Xu M, Yuan C, et al. Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-κB and activator protein-1. Int J Biochem Cell Biol. 2013; 45(7): 1366–1376.
  24. Doucet C, Brouty-Boyé D, Pottin-Clémenceau C, et al. Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. J Clin Invest. 1998; 101(10): 2129–2139.
  25. Brouty-Boyé D, Pottin-Clémenceau C, Doucet C, et al. Chemokines and CD40 expression in human fibroblasts. Eur J Immunol. 2000; 30(3): 914–919.
  26. Sato T, Kotake D, Hiratsuka M, et al. Enhancement of inflammatory protein expression and nuclear factor Κb (NF-Κb) activity by trichostatin A (TSA) in OP9 preadipocytes. PLoS One. 2013; 8(3): e59702.
  27. Roger T, Lugrin J, Le Roy D, et al. Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection. Blood. 2011; 117(4): 1205–1217.
  28. Rafehi H, Balcerczyk A, Lunke S, et al. Vascular histone deacetylation by pharmacological HDAC inhibition. Genome Res. 2014; 24(8): 1271–1284.
  29. Iwata K, Tomita K, Sano H, et al. Trichostatin A, a histone deacetylase inhibitor, down-regulates interleukin-12 transcription in SV-40-transformed lung epithelial cells. Cell Immunol. 2002; 218(1-2): 26–33.
  30. Angrisano T, Pero R, Peluso S, et al. LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes. BMC Microbiol. 2010; 10: 172.

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